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Protective Effect of Genistein on Condylar Cartilage through Downregulating NF-?B Expression in Experimentally Created Osteoarthritis Rats.

ABSTRACT: Temporomandibular joint osteoarthrosis (TMJOA) is characterised by chronic inflammatory changes, with subsequent gradual loss of joint cartilage. NF-?B is a crucial transcription factor in the course of inflammatory and immune responses, which are involved in OA pathology activated by proinflammatory cytokines. Genistein is known to have anti-inflammation and modulation of metabolic pathways through repression of the NF-?B signaling pathway in inflammatory disease. But so far, studies on the effects of genistein on TMJOA are very limited. So, the purpose of this study is to investigate the protective effect of genistein against experimentally induced condylar cartilage degradation through downregulating NF-?B expression in created osteoarthritis rats in vivo. Male SD rats were created as temporomandibular joint osteoarthritis models and administered through oral gavage with low and high dosage genistein (30?mg/kg and 180?mg/kg, respectively) daily for 4 weeks. The morphological changes of the condylar cartilage were studied with HE and Masson staining. The expressions of p65 and inflammatory cytokines (IL-1? and TNF?) were detected using immunohistochemistry and real-time PCR. The results showed that experimentally created osteoarthritis reduced the condylar cartilage thickness of rats and increased the gene expression of cytokines (IL-1? and TNF?) and positive cells of p65. Genistein treatment had positive effects on the condylar cartilage renovation, while high dose genistein treatment had more significant effects on the reversing of OA changes and reduction of the expression of p65 and inflammatory cytokines (IL-1? and TNF?). The results indicated that high dose genistein treatment had obvious therapeutic effects on condyle cartilage damages of OA rats. The mechanism may be that genistein suppresses the NF-?B expression activated by inflammatory cytokines.

SUBMITTER: Yuan J

PROVIDER: S-EPMC7011344 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Protective Effect of Genistein on Condylar Cartilage through Downregulating NF-κB Expression in Experimentally Created Osteoarthritis Rats.

Yuan Jian J Ding Wanghui W Wu Na N Jiang Shijie S Li Wen W

BioMed research international 20191230

Temporomandibular joint osteoarthrosis (TMJOA) is characterised by chronic inflammatory changes, with subsequent gradual loss of joint cartilage. NF-κB is a crucial transcription factor in the course of inflammatory and immune responses, which are involved in OA pathology activated by proinflammatory cytokines. Genistein is known to have anti-inflammation and modulation of metabolic pathways through repression of the NF-κB signaling pathway in inflammatory disease. But so far, stud ...[more]

PMID: 32083119

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Project description:The disorders of cartilage homeostasis and chondrocyte apoptosis are major events in the pathogenesis of osteoarthritis (OA). Herein, we aim to assess the chondroprotective effect and underlying mechanisms of a novel chemically modified curcumin, CMC2.24, in modulating extracellular matrix (ECM) homeostasis and inhibiting chondrocyte apoptosis. Rats underwent the anterior cruciate ligament transection, and medial menisci resection was treated by intra-articular injection with CMC2.24. In an in vitro study, rat chondrocytes were pretreated with CMC2.24 before stimulation with sodium nitroprusside (SNP). Results from in vivo studies demonstrated that the intra-articular administration of CMC2.24 ameliorated osteoarthritic cartilage destruction by promoting collagen 2a1 production and inhibited cartilage degradation and apoptosis by suppressing hypoxia-inducible factor-2a (Hif-2α), matrix metalloproteinase-3, runt-related transcription factor 2, cleaved caspase-3, and vascular endothelial growth factor and the phosphorylation of IκBα and NF-κB p65. The in vitro results revealed that CMC2.24 exhibited a strong inhibitory effect on SNP-induced chondrocyte catabolism and apoptosis. The SNP-enhanced expression of Hif-2α, a catabolic and apoptotic factor, decreased in a dose-dependent manner after CMC2.24 treatment. CMC2.24 pretreatment effectively inhibited SNP-induced IκBα and NF-κB p65 phosphorylation in rat chondrocytes, whereas pretreatment with the NF-κB antagonist BMS-345541 significantly enhanced the effects of CMC2.24. Overall, these results demonstrated that CMC2.24 attenuates OA progression by modulating ECM homeostasis and chondrocyte apoptosis by suppressing the NF-κB/Hif-2α axis, thus providing a new perspective for therapeutic strategies in OA. KEY MESSAGES: • Intra-articular injection of CMC2.24 ameliorated osteoarthritic cartilage destruction. • CMC2.24 promoted cell viability and decreased SNP-induced apoptotic gene expression. • SNP-induced activation of Hif-2α is inhibited by CMC2.24. • CMC2.24 inhibits NF-κB/Hif-2α axis activation to modulate ECM homeostasis and inhibit chondrocyte apoptosis.

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Dataset Information

Protective Effect of Genistein on Condylar Cartilage through Downregulating NF-?B Expression in Experimentally Created Osteoarthritis Rats.

Publications

Protective Effect of Genistein on Condylar Cartilage through Downregulating NF-<i>κ</i>B Expression in Experimentally Created Osteoarthritis Rats.

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